Alpha-fetoprotein (AFP) is a glycoprotein present in the serum and a classical oncofetal marker. This protein is expressed at high levels during fetal life in the liver and the visceral endoderm of the yolk sac, and at lower levels in the developing gastrointestinal tract (Andrews et al., 1982; Tilghman and Belayew 1982), in the adult serum only trace amount are detected (Tilghman and Belayew 1982). The protein expressed by the embryos is secreted and present in the maternal blood circulation during gestation, the level of AFP concentration in the maternal serum is use to detect fetuses with spina bifida or Down's syndrome. The reason for this altered AFP level associated with those pathologies are not understood, but they have been used extensively in prenatal screening. The synthesis of AFP decreases dramatically after birth and only trace amounts are detected in adult liver. However expression of afp is associated with hepatocarcinomas and liver regeneration induced by partial hepatectomy or acute tetrachloride (CC14) intoxication. The control of afp gene expression has thus attracted much attention and it has been shown that afp expression is regulated by transcriptional mechanisms involving a large promoter and three distant enhancers (review of Chen et al. (1997)). Because AFP is synthesized during the G1 and S phases, it has been hypothesized that intracellular AFP affects cell growth (Leffert and Sell, 1974; Sell et al., 1975; Tsukada and Hirai, 1975; Belanger et al., 1978). The observation that AFP is able to bind estrogen led to the suggestion that AFP plays a role in the control of cell metabolism. In addition to binding estrogen, AFP, like albumin to which it is evolutionary related, is able to bind other steroids and endogenous and exogenous substances such as fatty acids, billirubin and various pharmaceutical agents suggesting that AFP may play a general transportation function. For the fetus, in this respect, AFP could serve as a modulator/modifier of various cell growth regulatory pathways during embryonic and fetal development in vertebrates by interacting and/or binding cytoplasmic chaperone proteins that normally escort nuclear receptors or transcription co-factors through the cytoplasm towards organelle interfaces (Mizejewski, 1995, 1985). AFP has also been proposed to protect the embryo against the maternal immune system, on the basis of the observation that addition of purified AFP into the culture of splenic or lymphnode mononuclear cells exerts a suppressive effect on antibody synthesis.
The different hypotheses proposed for AFP function(s) can be focused on the fetal life (stage at which the gene is strongly transcripted) since the protein is described as a fetoprotein.
At the present time, no document of the state of the art has suggested that the alpha-fetoprotein may play an essential role for female reproduction and fertility.
Aims of the Invention
The present invention aim to provide new models (animal models) as well as new methods and devices for the study, the testing and/or the screening of fertility or contraception methods, compounds and compositions intended for adult mammals (including humans) and/or for the study, the testing and/or the screening of new methods, compounds or compositions intended for the treatment and/or the prevention of osteoporosis.